Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes
Authors: Nicola S. Meagher, Kylie L. Gorringe, Matthew Wakefield, Adelyn Bolithon, Chi Nam Ignatius Pang, Derek S. Chiu, Michael S. Anglesio, Kylie-Ann Mallitt, Jennifer A. Doherty, Holly R. Harris, Joellen M. Schildkraut, Andrew Berchuck, Kara L. Cushing-Haugen, Ksenia Chezar, Angela Chou, Adeline Tan, Jennifer Alsop, Ellen Barlow, Matthias W. Beckmann, Jessica Boros, David D.L. Bowtell, Alison H. Brand, James D. Brenton, Ian Campbell, Dane Cheasley, Joshua Cohen, Cezary Cybulski, Esther Elishaev, Ramona Erber, Rhonda Farrell, Anna Fischer, Zhuxuan Fu, Blake Gilks, Anthony J. Gill, Charlie Gourley, Marcel Grube, Paul R. Harnett, Arndt Hartmann, Anusha Hettiaratchi, Claus K. Høgdall, Tomasz Huzarski, Anna Jakubowska, Mercedes Jimenez-Linan, Catherine J. Kennedy, Byoung-Gie Kim, Jae-Weon Kim, Jae-Hoon Kim, Kayla Klett, Jennifer M. Koziak, Tiffany Lai, Angela Laslavic, Jenny Lester, Yee Leung, Na Li, Winston Liauw, Belle W.X. Lim, Anna Linder, Jan Lubiński, Sakshi Mahale, Constantina Mateoiu, Simone McInerny, Janusz Menkiszak, Parham Minoo, Suzana Mittelstadt, David Morris, Sandra Orsulic, Sang-Yoon Park, Celeste Leigh Pearce, John V. Pearson, Malcolm C. Pike, Carmel M. Quinn, Ganendra Raj Mohan, Jianyu Rao, Marjorie J. Riggan, Matthias Ruebner, Stuart Salfinger, Clare L. Scott, Mitul Shah, Helen Steed, Colin J.R. Stewart, Deepak Subramanian, Soseul Sung, Katrina Tang, Paul Timpson, Robyn L. Ward, Rebekka Wiedenhoefer, Heather Thorne, Paul A. Cohen, Philip Crowe, Peter A. Fasching, Jacek Gronwald, Nicholas J. Hawkins, Estrid Høgdall, David G. Huntsman, Paul A. James, Beth Y. Karlan, Linda E. Kelemen, Stefan Kommoss, Gottfried E. Konecny, Francesmary Modugno, Sue K. Park, Annette Staebler, Karin Sundfeldt, Anna H. Wu, Aline Talhouk, Paul D.P. Pharoah, Lyndal Anderson, Anna DeFazio, Martin Köbel, Michael L. Friedlander, Susan J. Ramus
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.